Breakthrough over growing human organs in animals
Scientists create hybrid embryos with stem cells from both species
Scientists have created hybrid embryos containing both human and sheep or pig cells in an early step toward growing human organs in farm animals before transplanting them into patients. Researchers from the US and Japan have succeeded in using stem cell and genomic editing technologies to transfer human cells into freshly generated sheep and goat embryos. They told the American Association for the Advancement of Science in Austin on Sunday that the chimeras, which contain cells from both species, developed for up to three weeks. Hiro Nakauchi, who pioneered the research at the University of Tokyo, grew a mouse with a rat pancreas and a rat with a mouse pancreas. When cells from the rat-grown mouse pancreas were transplanted into a diabetic mouse, they made enough insulin to cure the condition without being rejected. “The next step was to move into large animals,” Dr Nakauchi said. “This was prohibited in Japan so I decided to move to Stanford University in California to work with Professor Pablo Ross.”
Dr Nakauchi’s rodent work has demonstrated that you can “grow organs in a different species and cure a disease without [suppressing the immune system],” added Prof Ross, who is based at the University of California, Davis. “We are working together to translate the technology into humans, to solve the terrible shortage of organs for transplantation. In the US, 20 people die every day because they cannot get the organs they need.”
The research could breathe new life into the decades-old idea of xenotransplantation — growing organs such as hearts and kidneys in animals, particularly pigs, which would be harvested for human transplants. That idea was based on producing essentially porcine organs genetically engineered to make them acceptable to the human immune system. The new approach aims to create essentially human organs within animals, which should reduce the risk of rejection. It works by using new DNA editing technology, Crispr, to produce animal embryos that are genetically incapable of growing a particular organ — say, a pancreas. Then the embryos are injected with human stem cells. The overall proportion of human cells in the chimeric embryo may be small but, as it develops in the womb, the human cells fill the gap and produce the missing organ that the animal’s own genes cannot create.
“We have chosen to work with pigs and sheep because their organs are a similar size and shape to those of humans, and they grow quickly,” said Prof Ross. Development from new embryo to fully grown animal takes just nine months. Daniel Garry, professor of medicine at the University of Minnesota, is using a similar approach to tackle cardiovascular disease. Working with human-pig chimeras, he aims to create pigs that cannot make their own vasculature (heart and blood vessels). They would grow an equivalent system from human cells that could be harvested for transplantation.
In principle it would be possible to make organs genetically identical to patients, by converting their cells into an embryo-like state with “induced pluripotent stem cell” technology and then injecting them into a sheep or pig embryo. Or animals could be created with a genetically diverse range of human organs to match individual patients’ immune systems as closely as possible.
Although it may take many years to develop chimeric transplant technology to the stage where it could be used safely on patient, “things are moving fast,” said Prof Ross. “Ten years ago people said we were crazy to think of making rat pancreas in mice,” added Dr Nakauchi.
